Suppression of clofibrate-induction of peroxisomal and microsomal fatty acid-oxidizing enzymes by growth hormone and thyroid hormone in primary cultures of rat hepatocytes.

Using primary cultures of rat hepatocytes on a matri-gel, effects of peroxisome proliferator and omega-hydroxydodecanoic acid on cellular levels of acyl-CoA oxidase and CYP4A have been studied to determine the hormonal influence in serum-free media. Peroxisomal acyl-CoA oxidation, microsomal CYP4A content and laurate omega-hydroxylation were increased in rat hepatocytes by the addition of 100 microM clofibrate or Wy14,643 for two days. omega-Hydroxydodecanoic acid (100 microM) also increased peroxisomal acyl-CoA oxidation, but had no clear effect on microsomal CYP4A level and laurate omega-hydroxylation. CYP4A-mediated laurate omega-hydroxylation in hepatocytes was suppressed by the addition of pituitary growth hormone (0.05 mU/ml), but was not altered by the addition of triiodothyronine (30 nM). In contrast, clofibrate-mediated induction of acyl-CoA oxidase activity was decreased by the addition of either one of the hormones in hepatocytes. Suppression by those hormones was also observed with omega-hydroxydodecanoic acid-mediated induction of acyl-CoA oxidase activity. These results indicate the possibility that GH and T3 exert the suppressive effects on peroxisomal acyl-CoA oxidation through plural mechanisms with and without the alteration of CYP4A levels in livers.